POS0648 SEX DIFFERENCES IN ADVERSE DRUG REACTIONS FROM BIOLOGICAL USE IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY DISEASES
Authors: H. Gosselt, J. Van Lint, S. Tas, B. Van den Bemt, H. Vonkeman, F. Hoentjen, M. Nurmohamed, M. Van Doorn, N. Jessurun
Journal: Annals of the Rheumatic Diseases (2022)

Background Women generally report more adverse drug reactions (ADRs) than men. Information on sex differences concerning the frequency and the nature of ADRs is still limited and sex differences are often not considered in research on ADRs. Consequently, no sex specific distinction is made when reporting results of ADR analyses or when providing information to patients. Objectives To examine sex differences in regard to the nature and frequency of reported ADRs in patients with immune-mediated inflammatory disease (IMIDs) treated with adalimumab or etanercept. Methods Patients with rheumatoid arthritis (RA), psoriatic arthritis or axial spondyloarthritis using etanercept or adalimumab, were included from the Dutch Biologic Monitor (DBM). Questionnaires concerning experienced ADRs were filled out bimonthly. ADRs were coded according to Medical Dictionary for Regulatory Activities (MedDRA) terminology. Sex specific ADRs (e.g. concerning menstruation) were excluded. MedDRA Preferred Terms (PTs) were analyzed to assess the nature and frequency of ADRs. Only PTs that were reported at least four times were analyzed. Discrepancies in the distribution of the nature of reported ADRs between male and female patients were assessed using Fisher Freeman Halton with Monte Carlo simulation. Subsequently, differences in frequencies at PT level were examined using Fisher’s exact tests, corrected for multiple testing using Bonferroni correction. Results In total 748 consecutive patients were included of which the majority (59%) was female (Table 1). 362 participants (48%) reported at least one ADR during the study. Relatively more female patients (55%) reported at least one ADR compared to male patients (38%, p&lt;0.001). In total 882 ADRs were reported comprising 264 distinct ADRs, of which the majority (74%) was reported by female patients. The ADR distribution differed significantly between male and female patients (p=0.025). ‘Injection site pruritus’ (p=0.004), ‘injection site inflammation’ (p=0.028), ‘injection site hematoma’ (p=0.017), ‘injection site erythema’ (p=0.026), ‘hematoma’ (p=0.011) and ‘cystitis’ (p=0.044) were reported relatively more often by female patients (Figure 1). These differences were no longer statistically significant upon correction for multiple testing. Table 1. Demographics of included patients from the Dutch Biologic Monitor stratified on sex Participants Male Female N 304 444 Age, mean ± SD a 58.2 ± 11.9 56.6 ± 12.9 Indication b , N(% ) Bechterew’s disease/axial SpA 71 (23.4) 39 (8.8) Bechterew’s disease/axial SpA and PsA 4 (1.3) 8 (1.8) Bechterew’s disease/axial SpA and RA 8 (2.6) 3 (0.7) PsA 89 (29.3) 84 (18.9) RA 132 (43.4) 310 (69.8) bDMARDs, N(% ) Adalimumab 138 (45.4) 199 (44.8) Etanercept 159 (52.3) 232 (52.3) Switched adalimumab/etanercept 7 (2.3) 13 (2.9) Comedication, N(% ) c Methotrexate 107 (35.2) 250 (56.3) Corticosteroids 27 (8.9) 49 (11.0) Thiopurines 3 (1.0) 10 (2.2) Aminosalicylates 14 (4.6) 33 (7.4) a Age was missing for 1 male and 1 female patient. b Patients could report multiple indications. 5 male and 14 female participants also reported other indications. c Reported comedication is from the moment of inclusion. Eleven patients (male=3, female=8) did not start with etanercept or adalimumab at the moment they were included. For these, comedication is from the moment they reported to be treated with adalimumab or etanercept for the first time. Figure 1. Top reported ADRs Percentages on the x-axis were calculated separately for sex, divided by the number of male or female patients with at least one ADR. *p-value&lt;0.05. Conclusion Female patients reported relatively more ADRs than male patients. Also, the distribution of the nature of the ADRs significantly differed for male and female patients. In particular injection site reactions were reported relatively more often in female patients than in male patients. Therefore, sex differences in experiencing ADRs may exist and should be taken into consideration when investigating and reporting results on ADRs or when informing patients. Disclosure of Interests Helen Gosselt: None declared, Jette van Lint: None declared, Sander Tas Consultant of: Gebro, GSK, AbbVie, Galvani, Arthrogen/MeiraGTx, Galapagos, Grant/research support from: Pfizer, GSK, Celgene, BMS, Sanofi, AstraZeneca, Bart van den Bemt Speakers bureau: paid as speaker for UCB, Pfizer, Sanofi-Aventis, Galapagos, Amgen en Eli Lilly, Harald Vonkeman Speakers bureau: Amgen, BMS, Celgene, Galapagos, GSK, Janssen-Cilag, Lilly, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB, Grant/research support from: Abbvie, Sanofi-Genzyme, Frank Hoentjen Speakers bureau: Frank Hoentjen has served on advisory boards or as speaker for Abbvie, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, Consultant of: Celgene, Grant/research support from: Funding (Grants/Honoraria): Dr Falk, Janssen-Cilag, Abbvie, Takeda, Michael Nurmohamed Speakers bureau: Abbvie, Janssen, Celgene, Consultant of: Abbvie, Grant/research support from: Abbvie, Amgen, Pfizer, Galapagos, BMS, Martijn van Doorn Speakers bureau: Janssen, LEO Pharma, Pfizer, Novartis, Paid instructor for: LEO Pharma, Consultant of: AbbVie, Janssen, LEO Pharma, Pfizer, Celgene, Novartis, TEVA, MSD, Sanofi, AstraZeneca, Grant/research support from: Novartis, Janssen, Naomi Jessurun: None declared